Europium(III)-doped yttrium vanadate nanoparticles reduce the toxicity of cisplatin

Abstract

The aim of this study was to evaluate the antitumor efficiency of chemotherapy with cisplatin alone and incorporated into europium(III)-doped yttrium vanadate nanoparticles functionalized with 3‑chloropropyltrimethoxysilane with folic acid and without folic acid in a syngeneic mouse melanoma model. Histopathological, biochemical and genotoxic analyses of treated animals were performed to assess the toxicity of treatments. The treatment of the animals with cisplatin alone and the nanoparticles functionalized with cisplatin at a dose of 5 mg/kg b.w. for 5 days reduced tumor weight about 86% and 65%, respectively. Histopathological analysis showed lower mean frequency of mitoses in tumor tissue of the groups receiving cisplatin alone (90% reduction) and the nanoparticles functionalized with cisplatin (70% reduction) compared to the tumor control group. A reduction in body and liver weight and an increase in serum creatinine and urea levels were observed in animals treated with CDDP, but not in those receiving the nanoparticles functionalized with cisplatin. Genotoxicity assessment by the comet assay revealed lower frequencies of DNA damage in animals treated with the nanoparticles functionalized with cisplatin (mean score = 140.80) compared to those treated with cisplatin alone (mean score = 231.80). Marked toxic effects were observed in animals treated with cisplatin alone, while treatment with the nanoparticles functionalized with cisplatin showed no toxicity. Moreover, folic acid in the inorganic nanoparticles reduced the genotoxicity of cisplatin in the bone marrow micronucleus test (10 ± 1.4 and 40 ± 0.0 micronucleus, respectively). These results demonstrate the antitumor efficiency and significantly reduced systemic toxicity of the nanoparticles compared to CDDP.

Keywords: Antitumor activity; Cisplatin; Europium(III)-doped ytrrium vanadate; Folic acid; Inorganic nanoparticles; Toxicity.